In the electronics industry, manufacturers and developers have sought to increase product performance, speed and capacity, as well as the profits derived therefrom, through miniaturization. Likewise, the pharmaceutical, biotechnology and related industries have sought similar benefits through miniaturization and automation of operations and processes performed in those industries. Performance of more and more operations in less and less space has thus become of primary interest in these industries. Space, therefore, while perhaps not the final frontier, remains an area that invites substantial exploitation.
To achieve this miniaturization the biotechnology and pharmaceutical industries have recently applied some of the same technologies which proved effective in the electronics industry, such as photolithography, wet chemical etching, laser ablation, etc., to the microfabrication of fluidic devices for use in chemical and biological applications. For example, as early as 1979, researchers reported the fabrication of a miniature gas chromatograph on a silicon wafer (discussed in Manz et al., Adv. in Chromatog. (1993) 33:1-66, citing Terry et al., IEEE Trans. Electron. Devices (1979) ED-26:1880). These fabrication technologies have since been applied to the production of more complex devices for a wider variety of applications.
There have been additional reports of microfabrication of fluidic devices in these solid substrates for a variety of uses. The most prominent of uses for this technology has been in the area of microcapillary electrophoresis. Microcapillary electrophoresis typically involves the introduction of a macromolecule containing sample, e.g., nucleic acids or proteins, into one end of a capillary tube that also contains a separation medium such as agarose, polyacrylamide or the like. A potential is applied across the capillary to draw the sample through the channel, separating the macromolecules in the sample based upon their relative motility in the separation medium, which can vary by the size or charge on the macromolecules. While these methods typically employed fused silica capillaries for the performance of electrophoretic methods, in more recent efforts, the fused silica capillary has been replaced by an etched channel in a solid planar substrate. A covering substrate provides the last wall of the capillary. Early discussions of the use of planar chip technology for fabrication of microfluidic devices are provided in Manz et al., Trends in Anal. Chem. (1990) 10(5):144-149 and Manz et al., Adv. in Chromatog. (1993) 33:1-66, which describe the fabrication of fluidic devices and particularly microcapillary devices, in silicon and glass substrates.
The transport and direction of materials, e.g., fluids, samples, analytes, buffers and reagents, within microfabricated devices has generally been carried out by: (1) the incorporation of mechanical micropumps and valves within the device (see, Published U.K. Patent Application No. 2,248,891, Published European Patent Application No. 568,902, U.S. Pat. Nos. 5,271,724, 5,277,556 and 5,171,132); (2) the use of electric fields to move a fluid containing charged elements through the device (see, e.g., Published European Patent Application No. 376 611, Harrison et al., Anal. Chem. (1992) 64:1926-1932, Manz et al. J. Chromatog. (1992) 593:253-258, U.S. Pat. No. 5,126,022 to Soane); (3) the use of acoustic energy to move fluid samples within devices by the effects of acoustic means (see, Published PCT Application No. 94/05414 to Northrup and White); or (4) the application of external pressure to move fluids within the device (see, e.g., U.S. Pat. No. 5,304,487 to Wilding et al.).
As microfluidic systems become more complex, the ability to accurately control and direct the fluid flow within these systems becomes more and more difficult. It would therefore be desirable to provide improved microfluidic devices or systems that take into account the problems associated with these complex microfluidic systems. The present invention meets these and a variety of other needs.
The present invention is generally directed to microfluidic systems and methods for use in performing a plurality of parallel operations within a single microfluidic system. Such parallel analyses may be performed on a single sample material, or upon multiple sample materials.
In one aspect, the present invention provides a microfluidic device, that comprises a body structure, which includes a plurality of integrated microscale channels disposed therein. The plurality of integrated microscale channels include at least a first transverse channel, and at least first and second side channels disposed on a first side of the transverse channel. Each of the first and second side channels have first and second ends, where the first ends intersect the transverse channel, and the second ends are in electrical communication with at least a first electrode. Also included are at least third and fourth side channels disposed on a second side of the transverse channel. Each of the third and fourth side channels similarly have first and second ends, where the first ends intersect the transverse channel, and the second ends are in electrical communication with at least a second electrode. The side channels are provided whereby the electrical current path between the first electrode and the transverse channel through the first side channel provides substantially equal resistance to a resistance between the first electrode and the transverse channel through the second side channel.
The microfluidic devices described herein are generally useful for providing for controlled material transport within a large number of integrated channels, with a minimum of control nodes. For example, in a related aspect, the present invention provides a microfluidic device for controllably transporting material among a plurality of intersecting microscale channels. The device comprises a body structure having a channel network disposed therein. The channel network comprises a plurality of intersecting microscale channels, which include n channel intersections, and x unintersected channel termini, wherein n is greater than or equal to x, provided that x is at least 2 and n is at least 3. An electrical power supply is also included to supply a separate electrical potential to each of the unintersected termini, or electrical control nodes, of the plurality of microscale channels, whereby the electrical potential supplied at each of the x unintersected channel termini controls material transport at the n intersections. In preferred aspects, the power supply utilizes a controlled current at multiple electrodes to affect material transport. Examples of such power supplies are described in detail in U.S. application Ser. No. 08/678,436, filed Jul. 3, 1996, now U.S. Pat. No. 5,800,690 and International Patent Application No. PCT US97/12930, incorporated herein by reference.
In an additional related aspect, the present invention provides a microfluidic system, which includes a microfluidic device as described above. In particular, the system includes a microfluidic device that comprises a body structure having a plurality of integrated channels disposed in the body structure, the plurality of integrated channels. The integrated channels include at least a first transverse channel, and at least first and second side channels disposed on a first side of the transverse channel. Each of the first and second side channels have first and second ends, where the first ends intersect the transverse channel, and the second ends are in fluid communication with at least a first source of first material. Also included in the integrated channels are at least third and fourth side channels disposed on a second side of the transverse channel. Each of the third and fourth channels have first and second ends, where the first ends are in fluid communication with the transverse channel, and the second ends are in fluid communication with a waste reservoir. The system also includes a material transport system for transporting a second material into the transverse channel, and for transporting portions of the second material into the third and fourth channels. The transport is affected by directing a flow of first material from the first source, through the first and second channels into the transverse channel.
The present invention also provides methods of transporting materials in a serial to parallel material transport operation. In particular, the present invention provides a method of directing one or more materials serially introduced into a microscale channel, into a plurality of parallel channels fluidly connected to the microscale channel. The method comprises providing a microfluidic device having at lease a first microscale transverse channel, at least first and second microscale side channels intersecting a first side of the transverse channel, at least third and fourth microscale side channels intersecting a second side of the transverse channel. One or more materials are serially introduced into the first transverse channel. At least a portion of the one or more materials are then directed into the at least third and fourth channels by directing material into the transverse channel from the first and second channels.
In a further aspect, the present invention provides a method of controllably transporting a material among a plurality of interconnected microscale channels. The method comprises providing a microfluidic device having a body structure that includes a channel network disposed therein. The channel network includes a plurality of intersecting microscale channels, which comprise n channels and x unintersected channel termini, wherein x is less than or equal to n, and provided that x is at least 2 and n is at least 3. A separate selected electrical potential is applied to each of the x reservoirs, whereupon material is controllably moved at and through the n intersections.